Hi all, good luck with your coming consultations I have noted a few musings that may be of help.
David thanks for posting the recently updated guidelines these lay it out as it is at the moment at the clinical level. CLL treatment is an “ART” and Prof Fegan did speak recently at both the UK CLL Forum and the CLL open day at Cardiff. Both of his talks about expert clinical management had different flavours, The UK CLL Forum talk for the medics did give data showing that there was little difference in survival data between patients whose consultants had a special interest in CLL and there juniors or more general haematologists. However a Mayo study was discussed in which those treated by a consultant with a special interest gained better overall survival, however there was data missing and the cohort may have been self-selecting and a little self-serving. The message that came from both talks was that in the near future there will be much greater complexity involved in the treatment and accessing clinical trials because of the greater number of treatment trial options and available information an informed consultant with a special interest in CLL on your team will be of benefit not just because they are at the face of fast developing medicine but because they are most likely to be working out of trial centres and have access to all trials available.
Dr Annah Schuh is a clinical CLL researcher who is very involved with the new testing capabilities and their future integration into CLL medicine this is her recent paper:
State-of-the-Art Management of Patients Suffering from Chronic Lymphocytic Leukemia Abstract: “The management of chronic lymphocytic leukemia (CLL) has evolved dramatically in the last decade. For the first time, clinical intervention has been shown to alter the natural history of the disease. Considerable efforts are focussing on better patient selection and response prediction, and it is expected that the publication of the first 200 CLL genomes will spark new insights into risk stratification of CLL patients. Besides, many new agents are being evaluated on their own and in combination therapy in early and late Phase clinical studies. Here, we provide a general clinical introduction into CLL including diagnosis and prognostic markers followed by a summary of the current state-of-the-art treatment. We point to areas of continued clinical research in particular for patients with co-morbidities and highlight the challenges in managing refractory disease.”
Exerpt from Treatment:
General principles When to treat?
“The treatment of CLL poses many challenges, not least to convey to patients that no treatment is indicated for their newly diagnosed leukaemia. that no treatment is indicated. Although treatment indications have been clearly defined,2 the exact time when treatment should be initiated can be subjective and dependent more on severity of symptoms then objective criteria. In discussions with patients and relatives, the patient’s preference should be taken into consideration whenever possible, as CLL is a chronic cancerous condition that patients live with for years. A meta-analysis of initial studies using chlorambucil with or without prednisolone, did not show any benefit for early treatment versus watch and wait.31 This question is currently being revisited by the German CLL Study Group using modern chemoimmunotherapy versus watch and wait in high-risk disease.”
http://www.la-press.com/state-of-the-art-management-of-patients-suffering-from-chronic-lymphoc-article-a3097
Knowledge of CLL is growing rapidly with the expansion of genome testing. There are more known kareotypes not just the early gang of four. Recently discovered mutations may alter the expected behaviour of a given kareotype. CLL may carry several anomalies and can be atypical. Additional small mutations can make the disease behave in a benign or aggressive way. We know that the family of VH genes the cell is using is important also somatic mutations to the TP53. ATM, Splicesome, NOTCH1 regions etc, will alter the order of things. The description normal kareotype just means that they cannot or have not identified its type of mutations yet. FISH probes historically are set to look in regions where mutations are expected. Better testing techniques are now identifying addition regions where damage may be.
From my reading the most important mutation or deletion of consequence at the moment that may affect what and when you are treated is if a 17p deletion or tp53 mutation is detected pre-treatment by FISH testing. The physical and clinical features that determine how and when you are treated are set out in the new guidelines provided by David. Below are a few recent papers that show how as the picture unfolds the picture becomes more complicated and many more questions are raised.
This is a recent paper explains the discovery of several new mutations that affect the understanding of the order of things.
Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
http://www.nature.com/nature/journal/v475/n7354/pdf/nature10113.pdf
"Our study shows that there may not be a sharp dividing line between the more aggressive and less aggressive forms of CLL," said Thomas J. Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research and senior author of the study. "Instead, it seems that over time the leukemia cells of patients with indolent disease begin to use genes similar to those that are generally used by CLL cells of patients with aggressive disease. In other words, prior to requiring therapy, the patterns of genes expressed by CLL cells appear to converge, regardless of whether or not the patient had aggressive versus indolent disease at diagnosis."
Article...
http://www.sciencedaily.com/releases/2012/07/120727154020.htm
“We all know about deletions and genetic damage in CLL...
A new study finds chromosome 'gains' in 75% of CLL cases studied. These are segments of DNA in a chromosome that gets repeated in error. Like a book, with two page 24s. These new copy number variations were found on Chromosome 20 at position 20q13.12 in 19% of patients. So not only do we have deletions, we also have additions. What these mean, in CLL is unknown at this time “
http://annonc.oxfordjournals.org/content/23/8/2138.abstract
Enter your message...